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https://www.readbyqxmd.com/read/28521790/unintentional-drowning-role-of-medicinal-drugs-and-alcohol
#1
Tuulia Pajunen, Erkki Vuori, Frank F Vincenzi, Pirjo Lillsunde, Gordon Smith, Philippe Lunetta
BACKGROUND: Alcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates. METHODS: Drowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75...
May 19, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28514657/huntington-s-disease-ipsc-derived-brain-microvascular-endothelial-cells-reveal-wnt-mediated-angiogenic-and-blood-brain-barrier-deficits
#2
Ryan G Lim, Chris Quan, Andrea M Reyes-Ortiz, Sarah E Lutz, Amanda J Kedaigle, Theresa A Gipson, Jie Wu, Gad D Vatine, Jennifer Stocksdale, Malcolm S Casale, Clive N Svendsen, Ernest Fraenkel, David E Housman, Dritan Agalliu, Leslie M Thompson
Brain microvascular endothelial cells (BMECs) are an essential component of the blood-brain barrier (BBB) that shields the brain against toxins and immune cells. While BBB dysfunction exists in neurological disorders, including Huntington's disease (HD), it is not known if BMECs themselves are functionally compromised to promote BBB dysfunction. Further, the underlying mechanisms of BBB dysfunction remain elusive given limitations with mouse models and post-mortem tissue to identify primary deficits. We undertook a transcriptome and functional analysis of human induced pluripotent stem cell (iPSC)-derived BMECs (iBMEC) from HD patients or unaffected controls...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28487650/neuropsychological-testing-and-machine-learning-distinguish-alzheimer-s-disease-from-other-causes-for-cognitive-impairment
#3
Pavel Gurevich, Hannes Stuke, Andreas Kastrup, Heiner Stuke, Helmut Hildebrandt
With promising results in recent treatment trials for Alzheimer's disease (AD), it becomes increasingly important to distinguish AD at early stages from other causes for cognitive impairment. However, existing diagnostic methods are either invasive (lumbar punctures, PET) or inaccurate Magnetic Resonance Imaging (MRI). This study investigates the potential of neuropsychological testing (NPT) to specifically identify those patients with possible AD among a sample of 158 patients with Mild Cognitive Impairment (MCI) or dementia for various causes...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28456368/bone-penetrance-of-locally-administered-vancomycin-powder-in-a-rat-femur-fracture-model
#4
Zachary M Working, Hunter Frederiksen, Alex Drew, Catherine Loc-Carrillo, Erik N Kubiak
INTRODUCTION: Locally delivered, crystalline vancomycin has been suggested as a potential prophylactic measure against the development of deep and superficial surgical site infection. Clinical expectations regarding the duration and peak of drug concentration in local tissues following administration are unknown. Our goal was to develop concentration vs time curves for locally administered vancomycin powder in a high-energy, open femur fracture rat model in local tissues and to compare that data to two well performed similar, systemic administration studies...
April 21, 2017: Injury
https://www.readbyqxmd.com/read/28448548/altered-striatal-endocannabinoid-signaling-in-a-transgenic-mouse-model-of-spinocerebellar-ataxia-type-3
#5
Carmen Rodríguez-Cueto, Mariluz Hernández-Gálvez, Cecilia J Hillard, Patricia Maciel, Sara Valdeolivas, José A Ramos, María Gómez-Ruiz, Javier Fernández-Ruiz
Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice...
2017: PloS One
https://www.readbyqxmd.com/read/28421460/flow-arrest-intra-arterial-delivery-of-small-tat-decorated-and-neutral-micelles-to-gliomas
#6
Juliane Nguyen, Shaolie S Hossain, Johann R N Cooke, Jason A Ellis, Michael B Deci, Charles W Emala, Jeffrey N Bruce, Irving J Bigio, Robert M Straubinger, Shailendra Joshi
The cell-penetrating trans-activator of transcription (TAT) is a cationic peptide derived from human immunodeficiency virus-1. It has been used to facilitate macromolecule delivery to various cell types. This cationic peptide is capable of crossing the blood-brain barrier and therefore might be useful for enhancing the delivery of drugs that target brain tumors. Here we test the efficiency with which relatively small (20 nm) micelles can be delivered by an intra-arterial route specifically to gliomas. Utilizing the well-established method of flow-arrest intra-arterial injection we compared the degree of brain tumor deposition of cationic TAT-decorated micelles versus neutral micelles...
April 18, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28419874/oral-administration-of-a-specific-kynurenic-acid-synthesis-kat-ii-inhibitor-attenuates-evoked-glutamate-release-in-rat-prefrontal-cortex
#7
D M Bortz, H-Q Wu, R Schwarcz, J P Bruno
Cognitive deficits represent core symptoms in schizophrenia (SZ) and predict patient outcome; however, they remain poorly treated by current antipsychotic drugs. Elevated levels of the endogenous alpha7 nicotinic receptor negative allosteric modulator and NMDA receptor antagonist, kynurenic acid (KYNA), are commonly seen in post-mortem tissue and cerebrospinal fluid of patients with SZ. When acutely or chronically elevated in rodents, KYNA produces cognitive deficits similar to those seen in the disease, making down-regulation of KYNA, via inhibition of kynurenine aminotransferase II (KAT II), a potential treatment strategy...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28391443/non-human-primate-models-of-pd-to-test-novel-therapies
#8
REVIEW
Marc Morissette, Thérèse Di Paolo
Non-human primate (NHP) models of Parkinson disease show many similarities with the human disease. They are very useful to test novel pharmacotherapies as reviewed here. The various NHP models of this disease are described with their characteristics including the macaque, the marmoset, and the squirrel monkey models. Lesion-induced and genetic models are described. There is no drug to slow, delay, stop, or cure Parkinson disease; available treatments are symptomatic. The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-Dopa) still remains the gold standard symptomatic treatment of Parkinson...
April 8, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28362421/a-protocol-for-rapid-post-mortem-cell-culture-of-diffuse-intrinsic-pontine-glioma-dipg
#9
Grant L Lin, Michelle Monje
Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood brainstem tumor that carries a universally fatal prognosis. Because surgical resection is not a viable treatment strategy and biopsy is not routinely performed, the availability of patient samples for research is limited. Consequently, efforts to study this disease have been challenged by a paucity of faithful disease models. To address this need, we describe here a protocol for the rapid processing of post-mortem autopsy tissue samples in order to generate durable patient-derived cell culture models that can be used in in vitro assays or in vivo orthotopic xenograft experiments...
March 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28349246/suicide-patterns-in-children-and-adolescents-a-review-from-a-pediatric-institution-in-england
#10
Khairul Zainum, Marta C Cohen
Suicide is a catastrophic event to both families and communities yet it is potentially preventable. This study aims to determine incidence and patterns of suicide in children and young adolescents in our region, raise awareness of this entity as a potentially preventable cause of death in this age group, and identify its possible associated risk factors. We retrospectively reviewed suicide cases presenting as sudden unexpected death in children and adolescents that underwent coronial post-mortems at our institution...
March 27, 2017: Forensic Science, Medicine, and Pathology
https://www.readbyqxmd.com/read/28345587/derivation-of-functional-human-astrocytes-from-cerebral-organoids
#11
Rômulo Sperduto Dezonne, Rafaela Costa Sartore, Juliana Minardi Nascimento, Verônica M Saia-Cereda, Luciana Ferreira Romão, Soniza Vieira Alves-Leon, Jorge Marcondes de Souza, Daniel Martins-de-Souza, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes
Astrocytes play a critical role in the development and homeostasis of the central nervous system (CNS). Astrocyte dysfunction results in several neurological and degenerative diseases. However, a major challenge to our understanding of astrocyte physiology and pathology is the restriction of studies to animal models, human post-mortem brain tissues, or samples obtained from invasive surgical procedures. Here, we report a protocol to generate human functional astrocytes from cerebral organoids derived from human pluripotent stem cells...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28340719/application-of-a-rapid-%C3%AE-spe-clean-up-for-multiclass-quantitative-analysis-of-sixteen-new-psychoactive-substances-in-whole-blood-by-lc-ms-ms
#12
Camilla Montesano, Gabriele Vannutelli, Valeria Piccirilli, Manuel Sergi, Dario Compagnone, Roberta Curini
Europe is an important market for illegal drugs, and nowadays a lot of new different psychoactive substances (NPS) are widespread. This work reports the development of a method to determine simultaneously different classes of NPS, as synthetic cannabinoids (SC) and their metabolites, cathinones and phenetylamines, directly on whole blood (WB) without anti-coagulants and using miniaturized solid phase extraction (μ-SPE). In order to demonstrate the feasibility of the method 16 different NPS belonging to the mentioned classes were selected for the analysis...
May 15, 2017: Talanta
https://www.readbyqxmd.com/read/28339816/post-mortem-toxicology-in-young-sudden-cardiac-death-victims-a-nationwide-cohort-study
#13
Thea Bjune, Bjarke Risgaard, Line Kruckow, Charlotte Glinge, Ole Ingemann-Hansen, Peter Mygind Leth, Kristian Linnet, Jytte Banner, Bo Gregers Winkel, Jacob Tfelt-Hansen
Aims: Several drugs increase the risk of ventricular fibrillation and sudden cardiac death (SCD). We aimed to investigate in detail the toxicological findings of all young SCD throughout Denmark. Methods and results: Deaths in persons aged 1-49 years were included over a 10-year period. Death certificates and autopsy reports were retrieved and read to identify cases of sudden death and establish cause of death. All medico-legal autopsied SCD were included and toxicological reports collected...
February 27, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28335036/validated-method-for-the-screening-and-quantification-of-baclofen-gabapentin-and-pregabalin-in-human-post-mortem-whole-blood-using-protein-precipitation-and-liquid-chromatography-tandem-mass-spectrometry
#14
Limon Nahar, Amy Smith, Rajan Patel, Rebecca Andrews, Sue Paterson
There has been a rapid increase in the number of prescriptions for baclofen (BLF), gabapentin (GBP) and pregabalin (PGL) in the UK since their introduction to therapy. Recent studies across the European Union and USA have shown the illicit abuse potential of these drugs and deaths have been observed. A simple, reliable and fully validated method was developed for the screening and quantification of BLF, GBP and PGL in human post-mortem (PM) blood. The analytes and their deuterated analogs as internal standard were extracted from blood using a single addition acetonitrile protein precipitation reaction followed by analysis using liquid chromatography-tandem mass spectrometry (LC-MS-MS) with triggered dynamic multiple reaction monitoring mode for simultaneous confirmation and quantification...
June 1, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28276094/pathology-of-toxic-leucoencephalopathy-in-drug-abuse-supports-hypoxic-ischemic-pathophysiology-etiology
#15
Murad Alturkustani, Lee-Cyn Ang, David Ramsay
The histopathological features of leucoencephalopathy caused by illicit drugs (such as opioids and cocaine) are well documented in acute cases but not in long-survival cases. There are several hypotheses about the pathogenesis of this disorder, including hypoperfusion, direct drug toxicity resulting from the neurotoxic effects of the drug itself or contaminants in the illicit drug vehicle. We reviewed the post mortem findings in five males (aged 24 to 56 years, with survival intervals ranging from 7 days to 5 months) with a history of illicit drug use and concomitant fatal white matter changes...
March 9, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28270242/to-see-or-not-to-see-non-invasive-imaging-for-improved-readout-of-drug-treatment-trials-in-the-murine-model-of-secondary-alveolar-echinococcosis
#16
D Gorgas, N Marreros, R Rufener, A Hemphill, B Lundström-Stadelmann
Alveolar echinococcosis (AE) is an emerging zoonotic disease caused by the cestode Echinococcus multilocularis. The secondary infection model of AE is based on intraperitoneal injection of disease-causing metacestodes into the peritoneal cavity of mice, which allows investigations on novel drugs or immunotherapeutical treatment options in vivo. So far, such in vivo studies assessed exclusively the parasite weight at the endpoint of a given treatment period. We here developed an ultrasound (US)-based scoring system that allows to follow-up parasite development in the living animal, and provides insights into parasite growth during the treatment phase...
March 8, 2017: Parasitology
https://www.readbyqxmd.com/read/28260886/convection-enhanced-delivery-of-panobinostat-lbh589-loaded-pluronic-nano-micelles-prolongs-survival-in-the-f98-rat-glioma-model
#17
W G Singleton, A M Collins, A S Bienemann, C L Killick-Cole, H R Haynes, D J Asby, C P Butts, M J Wyatt, N U Barua, S S Gill
BACKGROUND: The pan-histone deacetylase inhibitor panobinostat is a potential therapy for malignant glioma, but it is water insoluble and does not cross the blood-brain barrier when administered systemically. In this article, we describe the in vitro and in vivo efficacy of a novel water-soluble nano-micellar formulation of panobinostat designed for administration by convection enhanced delivery (CED). MATERIALS AND METHODS: The in vitro efficacy of panobinostat-loaded nano-micelles against rat F98, human U87-MG and M059K glioma cells and against patient-derived glioma stem cells was measured using a cell viability assay...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28241065/repeated-dexamphetamine-treatment-alters-the-dopaminergic-system-and-increases-the-phmri-response-to-methylphenidate
#18
Anouk Schrantee, Jordi L Tremoleda, Marzena Wylezinska-Arridge, Valentine Bouet, Peter Hesseling, Gideon F Meerhoff, Kora M de Bruin, Jan Koeleman, Thomas Freret, Michel Boulouard, Emilie Desfosses, Laurent Galineau, Alessandro Gozzi, François Dauphin, Willy Gsell, Jan Booij, Paul J Lucassen, Liesbeth Reneman
Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function...
2017: PloS One
https://www.readbyqxmd.com/read/28192174/does-genetic-bdnf-deficiency-in-rats-interact-with-neurotransmitter-control-of-prepulse-inhibition-implications-for-schizophrenia
#19
Maarten van den Buuse, Davina Biel, Kathrin Radscheit
Several studies have suggested a role of BDNF in the development of schizophrenia. For example, post-mortem studies have shown significantly reduced levels of BDNF protein expression in the brain of schizophrenia patients. We investigated the relationship between reduced levels of BDNF in the brain and the regulation of prepulse inhibition (PPI), a behavioral endophenotype of schizophrenia. We used BDNF heterozygous mutant rats which display a 50% decrease of mature BDNF protein levels. Previously, we observed normal baseline PPI and responses to the dopamine D1/D2 receptor agonist, apomorphine, in these rats...
April 3, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28138041/translational-pharmacology-of-the-mglur2-preferring-agonist-ly2812223-in-animal-and-human-brain
#20
Christian C Felder, Douglas A Schober, Yuan Tu, Anne T Quets, Hongling Xiao, Marla Watt, Edward R Siuda, Eric S Nisenbaum, Chuanix Xiang, Beverly Heinz, Lourdes Prieto, David L Mc Kinzie, James A Monn
LY2812223 was identified via structure-activity studies arising from the potent mGlu2/3 receptor agonist LY354740 as a selective mGlu2 agonist. This pharmacology was determined using cells stably transfected cells either containing the human mGlu2 or mGlu3 receptor. We extended the pharmacological evaluation of LY2812223 to native brain tissues derived from relevant species used for preclinical drug development as well as human post mortem brain tissue. This analysis was conducted to ensure pharmacological translation from animals to human subjects in subsequent clinical studies...
January 30, 2017: Journal of Pharmacology and Experimental Therapeutics
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